MetadataShow full item record
AbstractThe human LINE-1 (or L1) element is a non-LTR retrotransposon that is mobilized through an RNA intermediate by an L1-encoded reverse transcriptase and other L1-encoded proteins. L1 elements remain actively mobile today and continue to mutagenize human genomes. Importantly, when new insertions disrupt gene function, they can cause diseases. Historically, L1s were thought to be active in the germline but silenced in adult somatic tissues. However, recent studies now show that L1 is active in at least some somatic tissues, including epithelial cancers. In this review, we provide an overview of these recent developments, and examine evidence that somatic L1 retrotransposition can initiate and drive tumorigenesis in humans. Recent studies have: (i) cataloged somatic L1 activity in many epithelial tumor types; (ii) identified specific full-length L1 source elements that give rise to somatic L1 insertions; and (iii) determined that L1 promoter hypomethylation likely plays an early role in the derepression of L1s in somatic tissues. A central challenge moving forward is to determine the extent to which L1 driver mutations can promote tumor initiation, evolution, and metastasis in humans. Copyright 2017 by the authors.
SponsorsThis work was funded by the following National Institutes of Health grants: T32 CA154274 (E.C.S.), R01 CA166661 (S.E.D.), and R01 HG002898 (S.E.D.)
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85020393752&doi=10.3390%2fv9060131&partnerID=40&md5=3beac711411143a23c7d3f1b0f9cfee4; http://hdl.handle.net/10713/10978
- Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.
- Authors: Tubio JMC, Li Y, Ju YS, Martincorena I, Cooke SL, Tojo M, Gundem G, Pipinikas CP, Zamora J, Raine K, Menzies A, Roman-Garcia P, Fullam A, Gerstung M, Shlien A, Tarpey PS, Papaemmanuil E, Knappskog S, Van Loo P, Ramakrishna M, Davies HR, Marshall J, Wedge DC, Teague JW, Butler AP, Nik-Zainal S, Alexandrov L, Behjati S, Yates LR, Bolli N, Mudie L, Hardy C, Martin S, McLaren S, O'Meara S, Anderson E, Maddison M, Gamble S, Foster C, Warren AY, Whitaker H, Brewer D, Eeles R, Cooper C, Neal D, Lynch AG, Visakorpi T, Isaacs WB, Veer LV, Caldas C, Desmedt C, Sotiriou C, Aparicio S, Foekens JA, Eyfjörd JE, Lakhani SR, Thomas G, Myklebost O, Span PN, Børresen-Dale AL, Richardson AL, Van de Vijver M, Vincent-Salomon A, Van den Eynden GG, Flanagan AM, Futreal PA, Janes SM, Bova GS, Stratton MR, McDermott U, Campbell PJ, ICGC Breast Cancer Group., ICGC Bone Cancer Group., ICGC Prostate Cancer Group.
- Issue date: 2014 Aug 1
- L1 Mosaicism in Mammals: Extent, Effects, and Evolution.
- Authors: Faulkner GJ, Garcia-Perez JL
- Issue date: 2017 Nov
- Immune signatures correlate with L1 retrotransposition in gastrointestinal cancers.
- Authors: Jung H, Choi JK, Lee EA
- Issue date: 2018 Aug
- L1 retrotransposition in nondividing and primary human somatic cells.
- Authors: Kubo S, Seleme MC, Soifer HS, Perez JL, Moran JV, Kazazian HH Jr, Kasahara N
- Issue date: 2006 May 23
- Extensive somatic L1 retrotransposition in colorectal tumors.
- Authors: Solyom S, Ewing AD, Rahrmann EP, Doucet T, Nelson HH, Burns MB, Harris RS, Sigmon DF, Casella A, Erlanger B, Wheelan S, Upton KR, Shukla R, Faulkner GJ, Largaespada DA, Kazazian HH Jr
- Issue date: 2012 Dec